Factor VIII/von Willebrand factor (FVIII/vWF) is a large glycoprotein with which FVIII procoagulant and vWF activities are associated. The separation of the FVIII procoagulant activity from the vWF activity by a variety of methods coupled with the difficulty in isolating the protein associated with the FVIII procoagulant activity has led to considerable controversy about the molecular structure of FVIII/VWF. To help resolve this controversy, FVIII/vWF will be purified to homogeneity. Then further attempts will be made to isolate enough of the FVIII procoagulation protein, for example by sucrose density gradient untracentrifugation, to permit biochemical characterization. Since some of our recent experiments strongly suggest that modification by thrombin may be necessary for the generation of FVIII procoagulant activity, the reaction between thrombin and FVIII/vWF will be further examined by a variety of methods. Also subunits of FVIII/vWF produced by reduction and alkylation and fragments produced by cyanogen bromide or enzymatic cleavage will be separated and analyzed for functional activity and antigenicity.